What is it about?

Proteins can function when in their normal, soluble state, and cease to function when in any other state. The official narrative has been that when proteins become aggregated, they turn toxic. But a review of data in humans affected by Alzheimer's disease, the most common neurodegenerative disorder, the problem is that amyloid-beta, a key protein for normal brain health, depletes as it transforms into amyloid, cross-beta sheets of stable, non-functioning protein.

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Why is it important?

We reviewed data to show that the problem in neurodegeneration is the loss of normal protein rather than its accrual into "toxic proteinopathy." This opens a completely different therapeutic strategy: replacing normal protein to levels above a compensation threshold. This would represent a major departure from the decades-old approach to Alzheimer's and other neurodegenerative disorders, centered on anti-amyloid approaches, which have yielded futility or harm.


I hope this article opens researchers and foundations to the neglected "other side" of the Alzheimer's story. Evolutionary biology and Occam's razor converge on the observation that brain proteins are too important to readily turn into toxins. We must instead figure out why humans are losing these normal proteins to aggregation forces, and what to do to mitigate the functional loss that comes with it.

Alberto Espay
University of Cincinnati

Read the Original

This page is a summary of: Soluble Amyloid-β Consumption in Alzheimer’s Disease, Journal of Alzheimer s Disease, August 2021, IOS Press, DOI: 10.3233/jad-210415.
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